|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4ttv' size='340' side='right'caption='[[4ttv]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='4ttv' size='340' side='right'caption='[[4ttv]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ttv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TTV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TTV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ttv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TTV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TTV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BC9:(1R,2R)-2-[(2S,6E,8R,9S,11R,13S,15S,16S)-7-CYANO-8,16-DIHYDROXY-9,11,13,15-TETRAMETHYL-18-OXOOXACYCLOOCTADEC-6-EN-2-YL]CYCLOBUTANECARBOXYLIC+ACID'>BC9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BC9:(1R,2R)-2-[(2S,6E,8R,9S,11R,13S,15S,16S)-7-CYANO-8,16-DIHYDROXY-9,11,13,15-TETRAMETHYL-18-OXOOXACYCLOOCTADEC-6-EN-2-YL]CYCLOBUTANECARBOXYLIC+ACID'>BC9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TARS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ttv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ttv OCA], [https://pdbe.org/4ttv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ttv RCSB], [https://www.ebi.ac.uk/pdbsum/4ttv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ttv ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Threonine--tRNA_ligase Threonine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.3 6.1.1.3] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ttv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ttv OCA], [http://pdbe.org/4ttv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ttv RCSB], [http://www.ebi.ac.uk/pdbsum/4ttv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ttv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SYTC_HUMAN SYTC_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Threonine--tRNA ligase]]
| + | [[Category: Fang P]] |
| - | [[Category: Fang, P]] | + | [[Category: Guo M]] |
| - | [[Category: Guo, M]] | + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Ligase-antibiotic complex]]
| + | |
| - | [[Category: Macrolide]]
| + | |
| - | [[Category: Synthetase]]
| + | |
| - | [[Category: Trna]]
| + | |
| Structural highlights
Function
SYTC_HUMAN
Publication Abstract from PubMed
Aminoacyl-tRNA synthetases (AARSs) catalyze an early step in protein synthesis, but also regulate diverse physiological processes in animal cells. These include angiogenesis, and human threonyl-tRNA synthetase (TARS) represents a potent pro-angiogenic AARS. Angiogenesis stimulation can be blocked by the macrolide antibiotic borrelidin (BN), which exhibits a broad spectrum toxicity that has discouraged deeper investigation. Recently, a less toxic variant (BC194) was identified that potently inhibits angiogenesis. Employing biochemical, cell biological, and biophysical approaches, we demonstrate that the toxicity of BN and its derivatives is linked to its competition with the threonine substrate at the molecular level, which stimulates amino acid starvation and apoptosis. By separating toxicity from the inhibition of angiogenesis, a direct role for TARS in vascular development in the zebrafish could be demonstrated. Bioengineered natural products are thus useful tools in unmasking the cryptic functions of conventional enzymes in the regulation of complex processes in higher metazoans.
Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor.,Mirando AC, Fang P, Williams TF, Baldor LC, Howe AK, Ebert AM, Wilkinson B, Lounsbury KM, Guo M, Francklyn CS Sci Rep. 2015 Aug 14;5:13160. doi: 10.1038/srep13160. PMID:26271225[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mirando AC, Fang P, Williams TF, Baldor LC, Howe AK, Ebert AM, Wilkinson B, Lounsbury KM, Guo M, Francklyn CS. Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. Sci Rep. 2015 Aug 14;5:13160. doi: 10.1038/srep13160. PMID:26271225 doi:http://dx.doi.org/10.1038/srep13160
|
